Estrogens are known to be etiologic in human breast cancer and also in human liver tumors. Estrogen can also adversely affect hepatic function in certain genetically susceptible women where it causes a disease called cholestatic jaundice of pregnancy. We have found that the liver of Armenian hamster is extraordinarily sensitive to the effects of exogenous estrogens. Therefore, this rodent can be used as a new experimental model to study how estrogen disrupts hepatobiliary function to cause icterus and how estrogen produces hepatic tumors. We have used primary tissue culture of liver cells from the Armenian hamster in an attempt to reproduce in vitro the pathophysiology observed in vivo after estrogen administration. As a control, we have used primary hepatic cultures obtained from Syrian hamsters because in this hamster administration of estrogen does not produce acute hepatic toxicity or chronic hepatocarcinogenesis. In general, we have not been able to reproduce in vitro the hepatocyte toxicity from estrogens that has been observed in vivo. A cytoplasmic inclusion body (related to the human hepatic inclusion body called Mallory body) has been observed to appear after treatment of primary cultures of Armenian hamster hepatocytes. Also, an aberrant response has been found in primary hepatocyte cultures obtained from Armenian hamsters previously treated with estrogen. We do not know what unknown factors are necessary in vitro to reproduce the known estrogen toxicity observed in vivo.